We are studying the molecular structure of histocompatibility antigens, tumor antigens, and T-cell receptors. A combination of protein and DNA sequencing, in conjunction with peptide and nucleotide synthesis, is being used in order to reach a better understanding of the molecular architecture of these important biological molecules. Oligonucleotide directed site mutagenesis has been employed to elucidate the role of individual amino acids on the function and expression of histocompatibility class I and II antigens. Synthetic peptides corresponding to oncogene structures such as myc and ras are being generated and antibodies are being made to study the role that these proteins play in transformation and in normal growth control. Homogeneous DNA sequences predicted to form aberrant helices with inserted bases and hairpin stem and loops are being crystallized. These are model structures that will help clarify why certain sequences have a much greater tendency to mutate than others.